Molecular tweaks to a known pesticide may make it effective at killing pests while keeping beneficial bugs— such as bumble bees—safe, say researchers.

Pyrethroid pesticides target the voltage-gated sodium channel, a protein found in nerve and muscle cells used for rapid electrical signaling. They basically work by binding to the voltage gate of the sodium channel and preventing it from closing.

The pesticides, which overstimulate the nervous system to eventually kill the insect, don’t have the same effect on humans and other mammals.

“For the first time we are showing that unique structural features in bee sodium channels interfere with the binding of tau-fluvalinate to bumble bee sodium channels,” says coauthor Ke Dong, an insect toxicologist and neurobiologist at Michigan State University.

“This opens the possibility of designing new chemicals that target sodium channels of pests but spare bees.”

Sodium channels are large transmembrane proteins of more than 2,000 amino acid residues. Scientists in Dong’s lab initially started with sodium channels from other bugs, such as mosquitoes, fruit flies, cockroaches, mites, and ticks to find where pyrethroids bind on insect sodium channels to effectively kill them.

“By examining wild mosquitoes that have become resistant to pyrethroids, we were able to help narrow down the potential sites on which to focus,” Dong says.

Specifically, in a previous study, researchers identified mutations that made the channels more resistant to pyrethroids. They identified two distinct binding sites on insect sodium channels and also uncovered the molecular differences between mammals’ and insects’ reactions to pyrethroids.

For the current study, the team focused on a longstanding enigma that bumble bees and honey bees are highly sensitive to most pyrethroids, but resistant to tau-fluvalinate, which is currently used to control agricultural pests and varroa mites—one of the biggest threats to bees worldwide.

The team discovered that the channel is resistant to tau-fluvalinate but sensitive to other pyrethroids. Further mutational analysis and computer modeling revealed that specific amino acid residues in bumble bee sodium channels are responsible for the selective toxicity.

Future research will examine sodium channels from various pest and beneficial insects to explore the features of pyrethroid binding sites, which could lay the groundwork for designing new and selective pesticides.

It also will shed light on how pests develop resistance to insecticides over time and how beneficial insects respond to them in the field.

Shaoying Wu, of Henan Agricultural University in China is the study’s lead author. He conducted the research in Dong’s lab as a visiting scholar. The National Institutes of Health and MSU AgBioResearch funded the work.